The anti-cytotoxic T lymphocyte-associated antigen 4 treatment tremelimumab outcomes were sustained in a small proportion of patients

medwireNews: Analysis of long-term follow-up data for advanced melanoma patients treated with tremelimumab adds support to use of antibodies against cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) alongside other immunotherapy agents.

Between 2002 and 2008, 143 patients with stage IIIC or IV disease participated in four phase I and II trials of tremelimumab, the majority of whom received 10 mg/kg every month or 15 mg/kg every 3 months.

Moreover, 1-, 3- and 5-year survival rates were estimated to be 50%, 27% and 20%, respectively, with 13 patients alive for at least 120 months, with an estimated survival probability of 16% for both 10 and 12.5 years.

Of 141 patients assessed, 13 achieved complete responses and nine a partial response, giving an overall objective response rate of 15.6%. Response lasted between 3 months and over 136 months; the median duration was 6.5 years.

But the researchers note that nine patients without an objective response survived for at least 5 years, including four patients who had stable disease during therapy. Indeed, one patient survived for more than 12 years despite experiencing progressive brain metastases 2 months after beginning tremelimumab and undergoing treatment for bowel and liver metastases.

Noting that tumour lesions may appear to increase in size due to massive infiltration of cytotoxic T lymphocytes rather than cancer growth, the researchers comment: “Thus, a lesion may qualify as progressive disease by WHO or RECIST guidelines, but the patient may potentially be a responder using immune-related response criteria.”

Writing in the European Journal of Cancer, the team emphasises that although tremelimumab is unlikely to now receive approval for single-use against advanced melanoma, it is now under investigation in combination with immune agonists and an anti-PD-L1antibody, with potential for use alongside molecularly targeted agents.

“CTLA-4 blockade with tremelimumab can lead to long-lasting, sustained anti-tumour responses lasting well beyond a decade in a small proportion of patients with metastatic melanoma, and will likely continue to play a role in combination with other immunotherapeutics in these patients”, they conclude.